The interactions of the catalytic (C) and GTP-binding (G/F) proteins of adenylate cyclase are important in understanding the mechanisms by which hormones, cholera toxin and other agents regulate adenylate cyclase. We are attempting to isolate and characterize C and G/F from various animal tissues. A variant strain of S49 mouse lymphoma cells which lack the GTP-binding protein allows us to assess the progress of purification of G/F. We have also used the S49 cells to identify factors which can be used to stabilize C. Separation of C and G/F from bovine brain has been achieved using a new zwitterionic detergent CHAPS. The method for preparation of C and G/F is an improvement over existing procedures.